Relations cellules endothéliales/substituts sanguins : implication des contraintes de cisaillement ou de l'hypoxie, et évaluation de la cytotoxicité d'hémoglobines de nouvelle génération

Abstract : Hemoglobin based oxygen carriers (HBOC), under development and evaluation, are potentially able to induce modifications of endothelial cells (EC) behaviour. We developed protocols to evaluate the role of three different parameters, like shear stress, hypoxia and HBOC presence on EC. Several factors, like oxidative stress, vasomotion and inflammation were studied using qPCR, EPR, flow cytometry and metabolites quantification. At first, we observed simultaneously the action of shear stress and HBOC (Dex-BTC Hb, Oxyglobin®, aa-Hb) on EC behaviour. Our results show how shear stress influences EC response face to HBOC. Then, we elaborated a hypoxia/reoxygenation protocol with HBOC. Using two different protocols of hypoxia (brief and chronic) we demonstrated that different mechanisms drive cell response. After 4 h of hypoxia, reoxygénation with blood substitutes induces a diminution of the inflammation engender by hypoxia. However, after 24 h of hypoxia, we observed an over inflammation whatever was the blood substitute used. In conclusion, among the three HBOC tested, we highlighted that the presence of dextran in Dex-BTC-Hb solutions makes Hb furtive for EC Hb detection mechanisms. Finally, we developed cytotoxicity tests on new Hb generation (PEG-Hb, octameric Hb) based on cellular viability and apoptosis-necrosis. These tests were encouraging for both Hb.
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Caroline Gaucher. Relations cellules endothéliales/substituts sanguins : implication des contraintes de cisaillement ou de l'hypoxie, et évaluation de la cytotoxicité d'hémoglobines de nouvelle génération. Autre. Université Henri Poincaré - Nancy 1, 2007. Français. ⟨NNT : 2007NAN10145⟩. ⟨tel-01748403⟩

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